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Laws mandating that women be informed of mammographic breast density (MBD) with their mammogram results may increase anxiety. We report on changes in self-reported levels of anxiety, worry about developing breast cancer (BC), as well as perceived risk of BC resulting from three MBD notification methods: usual care (mailed notification letter), enhanced care (usual care with MBD educational brochure), or interpersonal care (enhanced care with promotora education), among a Latina population. A randomized controlled clinical trial of three MBD notifications was performed among Latina women aged 40 to 74 years receiving screening mammography at a federally qualified health center (FQHC). Measures of anxiety, BC worry and perceived lifetime BC risk were assessed using a questionnaire. Anxiety was measured using the State-Trait Anxiety Inventory scale (STAI-S). The question: \"How frequently do you worry about getting breast cancer someday\" assessed BC worry. perceived lifetime risk of BC was rated between 0% (no chance) to 100% (definitely will get). Additional surveys were completed at two weeks to six months (T1) and one year (T2) after the intervention. 1332 Latina women were randomized between October 2016 and October 2019. At T0, 51.8% had moderate or severe anxiety. BC worry was reported to be sometimes/ often/ almost all the time among 41.3% of participants. 25.4% reported a perceived lifetime risk of developing BC of > 10%, compared with 6.6% with Gail model estimated lifetime risk score of > 10%. There was no significant difference in the proportion of patients who maintained low or had decrease in their levels of anxiety, BC worry or perceived risk from T0 to either T1 or T2 surveys between intervention groups. This Latina cohort had high levels of anxiety and BC worry which persisted regardless of intervention received. Future work is needed to improve our understanding of factors that could lower anxiety and BC worry and improve BC risk perception in this population.

Background Laws mandating that women be informed of mammographic breast density (MBD) with their mammogram results may increase anxiety. We report on changes in self-reported levels of anxiety, worry about developing breast cancer (BC), as well as perceived risk of BC resulting from three MBD notification methods: usual care (mailed notification letter), enhanced care (usual care with MBD educational brochure), or interpersonal care (enhanced care with promotora education), among a Latina population. Methods A randomized controlled clinical trial of three MBD notifications was performed among Latina women aged 40 to 74 years receiving screening mammography at a federally qualified health center (FQHC). Measures of anxiety, BC worry and perceived lifetime BC risk were assessed using a questionnaire. Anxiety was measured using the State-Trait Anxiety Inventory scale (STAI-S). The question: “How frequently do you worry about getting breast cancer someday” assessed BC worry. perceived lifetime risk of BC was rated between 0% (no chance) to 100% (definitely will get). Additional surveys were completed at two weeks to six months (T1) and one year (T2) after the intervention. Results 1332 Latina women were randomized between October 2016 and October 2019. At T0, 51.8% had moderate or severe anxiety. BC worry was reported to be sometimes/ often/ almost all the time among 41.3% of participants. 25.4% reported a perceived lifetime risk of developing BC of > 10%, compared with 6.6% with Gail model estimated lifetime risk score of > 10%. There was no significant difference in the proportion of patients who maintained low or had decrease in their levels of anxiety, BC worry or perceived risk from T0 to either T1 or T2 surveys between intervention groups. Conclusion This Latina cohort had high levels of anxiety and BC worry which persisted regardless of intervention received. Future work is needed to improve our understanding of factors that could lower anxiety and BC worry and improve BC risk perception in this population. Clinical trial registration ClinicalTrials.gov, NCT02910986. Registered on 22/09/2016.

Estrogen-receptor-negative breast cancer (BCER−) is mainly treated with chemotherapeutics. Leptin signaling can influence BCER− progression, but its effects on patient survival and chemoresistance are not well understood. We hypothesize that leptin signaling decreases the survival of BCER− patients by, in part, inducing the expression of chemoresistance-related genes. The correlation of expression of leptin receptor (OBR), leptin-targeted genes (CDK8, NANOG, and RBP-Jk), and breast cancer (BC) patient survival was determined from The Cancer Genome Atlas (TCGA) mRNA data. Leptin-induced expression of proliferation and chemoresistance-related molecules was investigated in triple-negative BC (TNBC) cells that respond differently to chemotherapeutics. Leptin-induced gene expression in TNBC was analyzed by RNA-Seq. The specificity of leptin effects was assessed using OBR inhibitors (shRNA and peptides). The results show that OBR and leptin-targeted gene expression are associated with lower survival of BCER− patients. Importantly, the co-expression of these genes was also associated with chemotherapy failure. Leptin signaling increased the expression of tumorigenesis and chemoresistance-related genes (ABCB1, WNT4, ADHFE1, TBC1D3, LL22NC03, RDH5, and ITGB3) and impaired chemotherapeutic effects in TNBC cells. OBR inhibition re-sensitized TNBC to chemotherapeutics. In conclusion, the co-expression of OBR and leptin-targeted genes may be used as a predictor of survival and drug resistance of BCER− patients. Targeting OBR signaling could improve chemotherapeutic efficacy.

Chronic subdural hematoma (cSDH) frequently presents with headache, but the relationship between hematoma size and headache is not well defined. This study aims to determine the relationship between total hematoma size and headache presentation in cSDH patients while identifying a critical size threshold for headache development. We retrospectively reviewed adult cSDH patients diagnosed at our institution from January 1st, 2023, to June 4th, 2025. Patients with a Glasgow Coma Score (GCS) below 14 or a history of ventricular shunt were excluded. Data collected included demographic information, hematoma laterality, maximum cSDH diameter, headache on presentation, and GCS. Hematoma thickness was defined as the sum of maximum cSDH diameter on both sides. Multivariable logistic regression and receiver operating characteristic (ROC) analysis were performed to assess the association between headache presentation and hematoma thickness. Among 341 eligible patients, 169 (49.6 %) presented with headache. Patients with headache had greater hematoma thickness (18.3 ± 10.7 mm vs. 15.1 ± 9.8 mm, p = 0.004) and more frequent midline shift (49 % vs. 32 %, p = 0.002). Multivariable analysis showed younger age (OR = 0.97; 95 %CI 0.95–0.99; p = 0.001) and larger hematoma thickness (OR = 1.03; 95 %CI 1.01–1.05; p = 0.029) were independently associated with headache. ROC analysis identified a hematoma thickness threshold of 12.5 mm (AUC = 0.596; 95 %CI 0.536–0.656, p = 0.002). Younger age and larger hematoma thickness were independently associated with headache in patients with cSDH, which is multifactorial. A critical hematoma size threshold of 12.5 mm was derived for headache development, beyond which stretching of pain-sensitive structures may become clinically apparent. •The etiology for headache in cSDH is multifactorial.•Age and hematoma size are independent predictors of headache in cSDH patients.•Headaches were more likely to occur above a hematoma size threshold of 12.5 mm.

PurposeThe Sangre Por Salud (SPS) Biobank was established to facilitate biomedical research opportunities for the Latino community by creating an easily accessible prospective cohort for scientists interested in studying health conditions and health disparities in this population.ParticipantsIndividuals self-identifying as Latino, aged 18–85 years, were prospectively recruited from the primary care Internal Medicine clinic at Mountain Park Health Center in Phoenix, Arizona. After obtaining informed consent, detailed medical history questionnaires were captured, and blood samples were obtained for common laboratory tests. Participants authorised the research team to access their electronic health records for research purposes. In addition, participants had serum, plasma and DNA samples isolated and stored at the Mayo Clinic Arizona Biorepository Laboratory for long-term storage and future access. As part of the study, participants consented and agreed to be contacted for potential participation in future research studies.Findings to date3756 participants provided informed consent, of whom 3733 completed all study questionnaires, an oral glucose tolerance test and had blood collected and stored. The SPS cohort is predominantly composed of females (72%), with a median age at time of consent of 42 years. All participants self-identified as Hispanic/Latino, 45% were married, 53% were employed for wages and 60% had less than a high school degree. Around 25% of participants met diagnostic criteria for overweight (BMI 25–29 kg/m2), and 49% met for obesity (BMI≥30 kg/m2). At time of recruitment, hypertension, hyperlipidaemia and depression affected 22%, 20% and 13% of the cohort, respectively.Future plansWe plan to regularly update the participants’ electronic health records and self-reported health data to longitudinal research. Additionally, we plan to obtain a more comprehensive genomic analysis on the entire cohort, ensuring greater research interest and investigation into the underlying genetic factors that contribute to disease susceptibility in this cohort.

In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.

Background/Objectives: Generous consumption of phytonutrient-rich foods, including blueberries, provides benefits to multiple physiologic and metabolic systems. This study explored the potential that regular, generous blueberry intake could favorably modulate fecal microbiome composition in sedentary older (>60 years) men and women with overweight or obesity (BMI ≥ 25 to 32 kg/m2). Methods: Participants (n = 55) were randomized to daily consumption of either lyophilized blueberry powder (equivalent to 1.5 cups of blueberries) or an indistinguishable placebo powder; both groups participated in weekly supervised exercise classes. Fecal samples were collected at 0 and 12 weeks and frozen. Following this, 16S rRNA gene sequencing was used to profile each participant’s fecal microbiome. Blood biomarkers of cardiometabolic health were measured via nuclear magnetic resonance spectroscopy (NMR) pre- and post-treatment. Results: Comparing the baseline and endpoint results for the blueberry (n = 15) and placebo (n = 19) groups, there were no significant overall compositional differences or differences in the level of diversity in the fecal microbiome. However, in subjects whose diet included blueberry powder, there was a significant enrichment (p = 0.049) in the relative abundance of Coriobacteriales incertae sedis, a taxonomic group of bacteria that facilitates the metabolism of dietary polyphenols. The placebo group exhibited significant reductions in total cholesterol, LDL-C, non-HDL-C, total LDL-P, large LDL-P, and ApoB, while the blueberry group exhibited significant reductions in total HDL-P and ApoA-I after 12 weeks compared to baseline. Conclusions: Generous blueberry consumption may upregulate the ability of the older human gut to utilize dietary polyphenols by altering the fecal microbiome. Longer, larger-scale studies with blueberries or blueberry powder are needed to observe improvements in cardiometabolic risk factors in older adults with overweight or obesity.

BackgroundStem-like progenitor exhausted CD8+ T cells (TPEX), located within the tumor-draining lymph nodes (TDLNs), are responsible for maintaining tumor-specific responses in cancer. Although cytokines such as interleukin (IL)-15 are known to expand CD8+ T-cell subsets, transforming growth factor (TGF)-β in the TDLN is known to arrest the egress of these TPEX to the tumor microenvironment. We hypothesized that combining IL-15 stimulatory and TGF-β blocking activity would boost antitumor responses mediated by TPEX in the TDLN.MethodsWe developed a bifunctional TGF-βRII/IL-15 protein complex (HCW9218) and evaluated its antitumor activity in two murine models of melanoma and breast cancer. Peripheral blood, TDLN and tumor-infiltrating CD8+ T cells were characterized by flow cytometry following a single subcutaneous dose (s.c.) of HCW9218. Transcription profiling of CD8+ T cells in both murine models was performed. Synergistic activity of HCW9218 with immune-checkpoint inhibitors (ICIs) was evaluated. Finally, safety and immune profiling in patients with chemo-refractory/relapsed solid tumors was performed in a Phase 1 dose-escalating trial.ResultsHCW9218 was capable of localizing to the TDLNs and tumors after s.c. administration, neutralized TGF-β, expanded TPEX in TDLNs, increased chemokine-expressing effectors in peripheral circulation and promoted their infiltration into murine tumors. These data were corroborated in RNA sequencing analysis of TDLNs. ICIs significantly enhanced the effects of HCW9218 on TPEX and synergistically improved HCW9218 antitumor efficacy in melanoma and reduced spontaneous lung metastasis in breast cancer models. In a Phase 1 clinical trial, HCW9218 monotherapy was well-tolerated, reduced serum TGF-β levels, promoted and sustained CD8+ T-cell expansion in peripheral blood and CD8+ T-cell infiltration in tumor biopsies. Stable disease was reported for four of six subjects (67%) with advanced ovarian cancer treated with HCW9218.ConclusionsOur findings demonstrate that combination therapy targeting immune cells critical for antitumor responses and blocking immune-suppressive environment significantly improves antitumor therapeutic efficacy. These findings provide a strong basis for using HCW9218 to enhance the efficacy of ICIs against solid tumors in the clinical setting.

Aerosol particles are an important part of the Earth climate system, and their concentrations are spatially and temporally heterogeneous, as well as being variable in size and composition. Particles can interact with incoming solar radiation and outgoing longwave radiation, change cloud properties, affect photochemistry, impact surface air quality, change the albedo of snow and ice, and modulate carbon dioxide uptake by the land and ocean. High particulate matter concentrations at the surface represent an important public health hazard. There are substantial data sets describing aerosol particles in the literature or in public health databases, but they have not been compiled for easy use by the climate and air quality modeling community. Here, we present a new compilation of PM2.5 and PM10 surface observations, including measurements of aerosol composition, focusing on the spatial variability across different observational stations. Climate modelers are constantly looking for multiple independent lines of evidence to verify their models, and in situ surface concentration measurements, taken at the level of human settlement, present a valuable source of information about aerosols and their human impacts complementarily to the column averages or integrals often retrieved from satellites. We demonstrate a method for comparing the data sets to outputs from global climate models that are the basis for projections of future climate and large-scale aerosol transport patterns that influence local air quality. Annual trends and seasonal cycles are discussed briefly and are included in the compilation. Overall, most of the planet or even the land fraction does not have sufficient observations of surface concentrations – and, especially, particle composition – to characterize and understand the current distribution of particles. Climate models without ammonium nitrate aerosols omit ∼ 10 % of the globally averaged surface concentration of aerosol particles in both PM2.5 and PM10 size fractions, with up to 50 % of the surface concentrations not being included in some regions. In these regions, climate model aerosol forcing projections are likely to be incorrect as they do not include important trends in short-lived climate forcers.